Although the risk for xerostomia has improved with use of intensity-modulated radiation therapy (IMRT), it remains one of the most common side effects after irradiation of nasopharyngeal carcinoma, mainly due to the close proximity of level II cervical lymph nodes to the parotid gland. This randomized phase 2 trial examined whether sparing of the superficial lobe of the parotid reduces xerostomia in patients receiving radiation for nasopharyngeal carcinoma.

Eighty-two patients were included for xerostomia analysis and randomized to receive either superficial parotid lobe–sparing intensity-modulated radiation therapy (SPLS-IMRT) or conventional IMRT. For all patients, the whole parotid including deep and superficial lobes was contoured and the optimization objective was V36Gy <40%. In the experimental arm, the objective for the superficial lobe was lower with V26Gy <30%.

At 12 months, the rate of xerostomia was significantly lower in the superficial lobe sparing arm (83.4% v 95%). Grade 3 xerostomia decreased from 12.5% to 0%. There were no differences in disease-free or overall survival between the arms. The study shows that sparing the superficial parotid lobe is a potential way to reduce xerostomia while maintaining target volume coverage for nasopharyngeal carcinoma.

Reference (Pub-Med Link): Huang, H., Miao, J., Xiao, X., et al. (2022). Impact on xerostomia for nasopharyngeal carcinoma patients treated with superficial parotid lobe-sparing intensity-modulated radiation therapy (SPLS-IMRT): A prospective phase II randomized controlled study. Radiotherapy and Oncology : Journal of the European Society for Therapeutic  Radiology and Oncology, 175, 1–9. https://doi.org/10.1016/j.radonc.2022.07.006

Key Institution: Sun Yat-sen University Cancer Center
Keywords: Head & Neck

Concurrent radio-chemotherapy is effective for head and neck cancer, but also has a lot of side effects. Therefore, there is some effort to de-escalate therapy for different sub-types. Patients with low risk nasopharyngeal cancer have excellent treatment outcomes and could potentially benefit from treatment de-intensification.

This randomized, phase 3, multicenter trial aimed to examine if radiation alone (RT) has non-inferior failure-free survival compared to chemoradiation (CRT) for endemic nasopharyngeal carcinoma. 341 patients were enrolled, who had cT2N0-1 or cT3N0 squamous cell carcinoma of the nasopharynx that was considered low-risk based on the following criteria: all nodes <3cm, no level IV or VB metastases, no ENE, and an EBV DNA titer <4000 copies/mL. Radiation in both arms was delivered using IMRT with 4 different dose levels including a prescribed dose of 68-70 Gy in 30-33 fractions to the primary lesion. Patients in the chemoradiation arm received 100 mg/m2 cisplatin every 3 weeks for 3 cycles.

After 46 months median follow-up, the rate of locoregional failure was 7.6% with radiation therapy alone and 6.5% with chemoradiation, and the rate of distant metastasis was 4.7% v 2.4%. The 3-year failure free survival was deemed non-inferior with radiation therapy alone compared with chemoradiation (90.5% v 91.9%). There was no difference in overall survival between radiation therapy alone and chemoradiation (98.2% v 98.6%). Quality of life outcomes were significantly better with radiation alone. The overall rate of grade 3-4 toxicity with radiation therapy alone was less than half that of concurrent chemoradiation (17% v 46%). These included lower rates of hematologic toxicity as well as less nausea/vomiting (1% v 15%), weight loss (1% v 5%), and mucositis (10% v 19%). The authors found no difference in late grade 3-4 toxicity.

In summary, early results of this trial indicate that omission of chemotherapy for early stage, low-risk nasopharyngeal carcinoma has similar 3-year failure free survival as chemoradiation.

(Open Access)

Reference (Pub-Med Link): Tang, L.-L., Guo, R., Zhang, N., et al. (2022). Effect of Radiotherapy Alone vs Radiotherapy With Concurrent Chemoradiotherapy on Survival Without Disease Relapse in Patients With Low-risk Nasopharyngeal Carcinoma: A Randomized Clinical Trial. JAMA, 328(8), 728–736. https://doi.org/10.1001/jama.2022.13997

Key Institution: Multi-Center, China
Keywords: Head & Neck

In head and neck cancer, especially in elderly patients who are not candidates for concurrent chemotherapy there is renewed interest in hypofractionated radiation therapy, however there is limited data and lack of consensus to support its use. Additionally, swallowing outcomes for patients treated with radiotherapy alone are poorly described compared with those treated with chemo-radiotherapy, largely because they represent a group under-represented in clinical trials.

This multi-center retrospective observational study in UK compared long term swallowing function as well as outcomes (i.e., LRC and OS) between patients treated with curative intent mild hypofractionation (65-66 Gy in 30 fx over 6 weeks) and standard fractionation (70 Gy in 35 fx over 7 weeks) radiation alone for locally-advanced oropharyngeal squamous cell carcinoma (OPSCC). Swallowing function was assessed using MD Anderson Dysphagia Inventory (MDADI) questionnaire, which was sent to patients alive and cancer-free at a minimum of 2 years post-radiotherapy (n = 151, 65%).

LRC and OS were similar across schedules (p = 0.78 and 0.95 respectively, log-rank test). Enteral feeding rates during radiotherapy appeared higher in the 7-week group though this did not reach statistical significance (59% vs 48%, p = 0.08). Feeding rates were similar at 1 year post radiotherapy for both groups (10% vs 6%, p = 0.27). 107 patients returned MDADI questionnaires (71%); there were no differences between the 6- and 7-week groups for median global (60.0 vs 60.0, p = 0.99) and composite (65.8 vs 64.2, p = 0.44) MDADI scores.

This observational study of patients with oropharyngeal cancer who were treated with radiation therapy only, suggests that treatment outcomes and long-term swallowing function after mild hypofractionation over six weeks are comparable to standard fractionation over seven weeks

Reference (Pub-Med Link): Price, J. M., West, C. M., Dixon, L. M., et al.  (2022). Similar long-term swallowing outcomes for accelerated, mildly-hypofractionated radiotherapy compared to conventional fractionation in oropharyngeal cancer: A multi-centre study. Radiotherapy and Oncology, 172, 111–117. https://doi.org/10.1016/j.radonc.2022.05.013

This publication reports the longer term follow-up from the previously reported 3-year follow up of this randomized phase III trial investigating induction chemotherapy with gemcitabine and cisplatin followed by chemoradiation for patients with locoregionally advanced nasopharyngeal cancer. The study involved patients treated with concurrent chemoRT alone (238 pts) versus gemcitabine and cisplatin followed by concurrent chemoRT (242 pts).

Previous 3-year overall survival was shown to be improved with induction chemotherapy followed by chemoRT (94% vs 93%) compared to chemoRT alone. This 5-year overall survival study continues to see this trend with 88% vs 79% overall survival, respectively. The authors were able to correlate tumor response with the induction chemotherapy to the overall survival. Patients who had complete response had 100% overall survival at 5 years. Patients with partial response and stable disease were less likely to survive at 5 years with 88% and 62% overall survival. The authors did a subset analysis of patients with low pre-treatment EBV and found that overall survival for this cohort of patients was not different between the induction chemo and chemoRT versus chemoRT alone (91% vs 91%).

Reference (Pub-Med Link): Zhang, Y., Chen, L., Hu, G.-Q., et al. (2022). Final Overall Survival Analysis of Gemcitabine and Cisplatin Induction  Chemotherapy in Nasopharyngeal Carcinoma: A Multicenter, Randomized Phase III Trial. Journal of Clinical Oncology, 40(22), 2420–2425. https://doi.org/10.1200/JCO.22.00327

Key Institution: Sun Yat-sen University Cancer Center and other hospitals in China
Keywords: H&N

In this retrospective nonrandomized study, the authors analyzed 1483 adult patients with nonmetastatic locally advanced cancers treated with concurrent chemotherapy between 2011 and 2016 at the University of Pennsylvania. 391 patients received proton therapy and 1092 received photon therapy. The main research question was whether proton therapy can reduce the risk of severe adverse events associated with unplanned hospitalizations compared to photon therapy for patients also receiving chemotherapy. The authors found that patients treated with protons tended to be older, with more medical comorbidities. Despite this, patients treated with protons had a lower risk of developing 90-day adverse events of at least grade 3, grade 2, and were less likely to have a decline in overall performance status. There was no difference in disease-free or overall survival. Although this does appear favorable for proton therapy, there are several important limitations. The study is retrospective and although the authors did use statistical techniques to try to account for potential sources of bias, there may be unmeasured differences between the groups, and randomize prospective studies are needed to confirm these results.

Reference (PubMed Link): Baumann BC, Mitra N, Harton JG, et al. Comparative effectiveness of proton vs photon therapy as part of concurrent chemoradiotherapy for locally advanced cancer. JAMA Oncol 2019;6:237-46.

Key Institution: U Pennsylvania
Keywords: Proton therapy, photon therapy, locally advanced cancer, concurrent chemoradiation